Effectiveness of Periocular Drug Injection in CATaract Surgery (EPICAT)

The ESCRS EPICAT Study: Effectiveness of Periocular Drug Injection in CATaract Surgery

Cystoid macular edema (CME) is a major cause of suboptimal postoperative visual acuity after cataract surgery. Topical steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs) are used to prevent CME. However, noncompliance with eye drops may compromise the effectiveness of treatment. Dropless periocular drug delivery during cataract surgery may improve the outcomes and cost-effectiveness of cataract surgery, and may alleviate the burden on homecare organizations.

Study Overview

• Status: Recruiting
• Conditions: Eye Diseases; Macular Edema; Cataract; Lens Diseases; Retinal Disease; Cystoid Macular Edema
• Intervention / Treatment: Drug: Bromfenac; Drug: Dexamethasone; Drug: Triamcinolone Acetonide; Drug: Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular Solution

Detailed Description

In a recent European multicentre study (PREvention of Macular EDema after cataract surgery; PREMED), it was demonstrated that the combination of topical corticosteroids and NSAIDs results in the lowest risk of developing CME after cataract surgery. However, noncompliance with eye drops may compromise the effectiveness of treatment. Noncompliance is often unintentional and related to forgetfulness or incorrect instillation, particularly in the elderly cataract surgery population.

The objective of this study is to evaluate the effectiveness of different treatments to prevent CME after cataract surgery, using either topical drugs (control group) or intra-/periocular injections (intervention groups).

The hypothesis of this study is that intra-/periocular anti-inflammatory drug delivery during cataract surgery is effective in preventing CME, with better health-related quality of life and improved cost-effectiveness compared to standard topical drug delivery.

The primary outcome measure is the change in central subfield mean macular thickness (CSMT) at 6 weeks postoperatively as compared to baseline. Secondary outcome measures are the incidence of CME; the incidence of clinically significant macular edema (CSME); mean corrected distance visual acuity (CDVA); para- and perifoveal thickness and total macular volume (TMV); intraocular pressure (IOP); anterior chamber inflammation; vision-related quality of life; and cost-effectiveness.

The design of this study is a European randomised controlled multicenter trial. The study population will consist of 808 patients aged 21 years or older who require cataract surgery in at least one eye. Patients with a foreseen increased risk of developing CME or ophthalmic disorders other than cataract will be excluded. Follow-up duration is 12 weeks. The study will be conducted over a period of 36 months.

• Study Type: Interventional
• Enrollment (Anticipated): 808
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Luigi UE Rondas, Drs.; Phone Number: +31 (0)43 387 1779; Email: luigi.rondas@mumc.nl

Study Locations

• Austria
  • Vienna, Austria, 1020
    • Not yet recruiting
    • Hospital of the Brothers of Saint John of God
  • Vienna, Austria, A-1140
    • Not yet recruiting
    • Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus
• Germany
  • Frankfurt am Main, Germany, 60590
    • Not yet recruiting
    • Goethe University
• Netherlands
  • Deventer, Netherlands, 7416SE
    • Recruiting
    • Deventer Ziekenhuis
  • Heerlen, Netherlands, 6419 PC
    • Recruiting
    • Zuyderland Medisch Centrum
    • Contact: Luigi Rondas, MSc; Phone Number: 0433871779; Email: luigi.rondas@mumc.nl
  • Maastricht, Netherlands, 6229HX
    • Recruiting
    • University Eye Clinic Maastricht UMC+
    • Contact: Luigi Rondas, MSc; Phone Number: 0433871779; Email: luigi.rondas@mumc.nl
  • Nijmegen, Netherlands, 6532SZ
    • Not yet recruiting
    • Canisius Wilhelmina Ziekenhuis Nijmegen
  • Tilburg, Netherlands, 5022GC
    • Recruiting
    • Elisabeth-Twee Steden Ziekenhuis, locatie Elisabeth
  • Zutphen, Netherlands, 7207AE
    • Recruiting
    • Gelre Ziekenhuizen
• Portugal
  • Coimbra, Portugal, 3000-075
    • Not yet recruiting
    • University Hospital Coimbra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• who are undergoing routine phacoemulsification (one eye per patient);
• who are 21 years or older;
• who should be able to communicate properly and understand instructions.
• willing and/or able to comply with the scheduled visits and other study procedures.

Exclusion Criteria:

• patients who already participated with their contralateral eye;
• combined surgery (e.g. combined phacoemulsification and trabeculectomy);
• patients with an increased risk of developing cystoid macular edema (CME) in the study eye (e.g. diabetes mellitus, previous retinal venous occlusion, or a history of uveitis, macular edema, epiretinal membrane, or previous retinal surgery);
• patients who developed CME after cataract surgery in the contralateral eye;
• patients with cystoid macular changes in the study eye at baseline;
• patients with an increased risk of developing perioperative complications (e.g. Fuchs' endothelial dystrophy);
• patients with permanent moderate visual impairment in the contralateral eye (decimal visual acuity less than 0.3);
• patients with a history of steroid induced IOP rise or glaucomatous visual field loss;
• patients using drugs that reduce or increase the risk of macular edema (e.g., periocular or intraocular corticosteroid, NSAID, or antivascular endothelial growth factor (VEGF) injection; topical corticosteroid or NSAID use; systemic corticosteroids (>= 20mg prednisolon), methotrexate, biologicals, or acetazolamide), or in the previous 4 months;
• patients with a contraindication for any of the investigated drugs;
• patients who are cardiovascular unstable;
• patients who have a history of hyperthyroidism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: topical bromfenac & dexamethasone; bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperatively & dexamethasone 0.1% eye drops four times daily starting two days before surgery and continuing four times daily during the first postoperative week and one drop less per day every following week.	Drug: Bromfenac; Bromfenac topical eye drops (Yellox); Other Names: Yellox; Product code: EU/1/11/692; Drug: Dexamethasone; Dexamethasone topical eye drops; Other Names: Dexamethasone ophthalmic solution; Product code (NL): RVG 56003
Active Comparator: subconjunctival triamcinolone acetonide; one subconjunctival injection of 10 mg triamcinolone acetonide during cataract surgery (TA, Triesence/Vistrec) in the inferotemporal quadrant, 6mm from the limbus.	Drug: Triamcinolone Acetonide; 0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally; Other Names: Triesence or Vistrec; Product code (NL): RVG 106092
Active Comparator: intracameral ketorolac; intracameral injection of ketorolac tromethamine solution during cataract surgery (Omidria). A 4ml vial of Omidria (ketorolac concentration 2.88mg/ml) is added to 500ml of the irrigation solution used during cataract surgery, resulting in a ketorolac concentration of 0.023mg/ml. At the end of the surgery, the anterior chamber will be filled with the ketorolac solution.	Drug: Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular Solution; Omidria is added to the irrigation fluid used during cataract surgery. At the end of surgery, the anterior chamber will be filled with the ketorolac solution.; Other Names: Omidria
Active Comparator: subconjunctival triamcinolone acetonide & intracameral ketorolac; one subconjunctival injection of 10 mg triamcinolone acetonide & intracameral injection of ketorolac tromethamine solution (Omidria; 0.023mg/mL) during cataract surgery.	Drug: Triamcinolone Acetonide; 0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally; Other Names: Triesence or Vistrec; Product code (NL): RVG 106092; Drug: Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular Solution; Omidria is added to the irrigation fluid used during cataract surgery. At the end of surgery, the anterior chamber will be filled with the ketorolac solution.; Other Names: Omidria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in central subfield mean macular thickness as a measurement of efficacy	The primary endpoint is the change in central subfield mean macular thickness in the 1 mm area (central subfield macular thickness, CSMT) as compared to baseline within the first 6 weeks postoperatively, measured using Optical Coherence Tomography (OCT)	Baseline, 6 weeks postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in central subfield mean macular thickness as a measurement of efficacy	Measured using OCT	Baseline, 12 weeks postoperatively
No. of subjects developing clinically significant macular edema as a measurement of efficacy	The occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively	Until 12 weeks postoperatively
Change in parafoveal retinal thickness in the central inner circle (1.0 - 3.0mm) as a measurement of efficacy	Measured using OCT	Baseline, 6 weeks and 12 weeks postoperatively
Change in perifoveal retinal thickness in the central outer circle (3.0 - 6.0mm) as a measurement of efficacy	Measured using OCT	Baseline, 6 weeks and 12 weeks postoperatively
Change in macular volume in the central 6.0mm area as a measurement of efficacy	Measured using OCT	Baseline, 6 weeks and 12 weeks postoperatively
Change in corrected distance visual acuity (CDVA) as a measurement of efficacy	CDVA measurements will be taken using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts (logMAR)	Baseline, 1 week, 6 weeks, and 12 weeks postoperatively
Change in Intraocular pressure (IOP) as a measurement of safety	IOP (in mmHg) will be measured by Goldmann applanation tonometry (preferred), Non-Contact Tonometry, or iCare tonometry	Baseline, 1 week, 6 weeks, and 12 weeks postoperatively
Anterior chamber inflammation as a measurement of safety	using the Standardization of Uveitis Nomenclature (SUN) classification	Baseline, 1 week , 6 weeks, and 12 weeks postoperatively
No. of subjects with Adverse Events as a measurement of safety and tolerability	An adverse event (AE) is defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the investigational product. All adverse events reported spontaneously by the subject or observed by the principal investigator or his staff will be recorded. Most frequently reported adverse events which might occur while using the study medication: abnormal sensation in the eye, pain or irritation, redness or headache while using eye drops; increased IOP and masking of infections while using corticosteroids; abnormal sensation in the eye, pain or irritation, conjunctival hyperaemia, inflammation and corneal edema after intracameral injection with phenylephrine/ketorolac.	Until 12 weeks postoperatively
Patient reported outcome measures (PROMs): NEI VFQ-25	Patient satisfaction and vision-specific quality of life as measured by National Eye Institute Visual Function Questionnaire (NEI VFQ-25).	Baseline and 12 weeks postoperatively
Patient reported outcome measures (PROMs): Catquest	Patient satisfaction and vision-specific quality of life as measured by Catquest questionnaire.	Baseline and 12 weeks postoperatively
Patient reported outcome measures (PROMs): HUI3	Health-related quality of life as measured by HUI3 (Health Utility Index Mark 3) questionnaire.	Baseline and 12 weeks postoperatively
Patient reported outcome measures (PROMs): EQ-5D-5L	Health-related quality of life as measured by EQ-5D-5L questionnaire.	Baseline and 12 weeks postoperatively
Quality Adjusted Life Years (QALYs)	Calculated based on generic health-related quality of life, using the EQ-5D-5L and HUI-3 questionnaires	Baseline until 12 weeks postoperatively
Costs per patient	Cost per patient, including valuation of resource use by using the Dutch guidelines for cost-analyses or cost prices provided by the medical center.	Baseline until 12 weeks postoperatively
Incremental cost-effectiveness ratios (ICERs): QALY	Evaluation of cost-effectiveness by using calculated costs per quality-adjusted life years (QALYs)	Baseline until 12 weeks postoperatively
Incremental cost-effectiveness ratios (ICERs): NEI VFQ-25	Calculated costs per clinically improved patient on the NEI VFQ-25 questionnaire	Baseline until 12 weeks postoperatively
Incremental cost-effectiveness ratios (ICERs): Catquest	Calculated costs per clinically improved patient on the Catquest questionnaire	Baseline until 12 weeks postoperatively
Incremental cost-effectiveness ratios (ICERs): Visual acuity	Calculated costs per patient with clinical improvement in (un)corrected distance visual acuity	Baseline until 12 weeks postoperatively
Budget impact	Reported as a difference in costs. Different scenario's will be compared to investigate the impact of various levels of implementation (e.g. 25%, 50%, 75% of eligible patients).	Baseline until 12 weeks postoperatively

Collaborators and Investigators

• Sponsor: Luigi Rondas
• Collaborators: European Society of Cataract and Refractive Surgeons
• Investigators: Principal Investigator: Nienke Visser, Dr., Universiteitskliniek voor Oogheelkunde Maastricht UMC+

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: November 21, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: December 2, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Prevention
• Additional Relevant MeSH Terms: Retinal Degeneration; Macular Degeneration; Retinal Diseases; Macular Edema; Eye Diseases; Cataract; Edema; Lens Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Dexamethasone; Dexamethasone acetate; BB 1101; Ketorolac; Ophthalmic Solutions; Triamcinolone; Pharmaceutical Solutions; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Bromfenac; Phenylephrine
• Other Study ID Numbers: NL72427.068.19; 2019-004890-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes